Coronary heart disease is generally caused by the narrowing of coronary arteries by atherosclerosis, the buildup of fatty deposits in the lining of the arteries. The process that may lead to atherosclerosis begins with the accumulation of excess fats and cholesterol in the blood. These substances infiltrate and deposit in the lining of arteries, gradually increase in size to form deposits commonly referred to as plaque or atherosclerotic occlusions. Plaques narrow the arterial lumen and impede blood flow. Blood cells may collect around the plaque, eventually creating a blood clot that may block the artery completely.
“Vulnerable plaque” is different from typical occlusive plaques that impede blood flow. Where occlusive plaques line the vessel lumen and physically obstruct the flow of blood, vulnerable plaques are developed within the arterial wall. Since vulnerable plaques do not result in lumen narrowing, patients with vulnerable plaque are often symptom free as compared to patients with typical occlusive atherosclerotic plaque. Consequently, detection of vulnerable plaque in patients creates a new challenge for the treatment of heart disease in recent years because conventional methods for detecting heart disease, such as an angiogram, may not detect vulnerable plaque growth in the arterial wall. Before the development of various experimental modalities to detect vulnerable plaque, only an autopsy, after death, can reveal the plaque congested in arterial wall that could not have been detected or seen otherwise.
The intrinsic histological features that may characterize a vulnerable plaque include increased lipid content, increased macrophage, foam cell and T lymphocyte content, and reduced collagen and smooth muscle cell (SMC) content. This fibroatheroma type of vulnerable plaque is often referred to as “soft,” having a large lipid pool of lipoproteins surrounded by a fibrous cap. The fibrous cap contains mostly collagen, but when combined with macrophage derived enzyme degradations, the fibrous cap can rupture under unpredictable circumstances. When ruptured, the lipid core contents, thought to include tissue factor, contact the arterial bloodstream, causing a blood clot to form that can completely block the artery resulting in an acute coronary syndrome (ACS) event. This type of atherosclerosis is termed “vulnerable” because of the unpredictable tendency of the plaque to rupture. It is thought that hemodynamic and cardiac forces, which yield circumferential stress, shear stress, and flexion stress, may cause disruption and contribute to mechanical rupture of the fibroatheroma type plaque. These forces may rise as the result of simple movements, such as getting out of bed in the morning, in addition to in vivo forces related to blood flow and the beating of the heart. It is thought that plaque vulnerability in fibroatheroma types is determined primarily by factors which include: (1) size and consistency of the lipid core; (2) thickness of the fibrous cap covering the lipid core; and (3) inflammation and repair within the fibrous cap.
FIG. 1A illustrates a section of a healthy artery 100 and FIG. 1B illustrates a cross-section of the same healthy artery 100. A healthy artery has a patent lumen 101. A monolayer of endothelial cells 102 covers the lining of the surface of the arterial lumen which is smooth and prevents blood clots. An artery is made of distinct layers. The internal elastic intima (IEL) 103 is an elastic layer just below the endothelial cells lining the arterial lumen. The media 104 consists mainly of muscle cells and extracellular matrix proteins and is located between the IEL and the external elastic lamina (EEL) 105. This muscular layer provides tone to the artery and controls the constriction and dilation of the artery. The EEL 105 separates the media from the adventitia 106. The adventitia is made of collagen and fibrous tissue and contains the vasa vasorum—which is a network of nerves, lymph vessels, and microarteries that supply oxygen, blood, and nutrients to the artery. When an artery is healthy, there is no or little atherosclerotic plaque deposited in the lumen and thus blood flows freely without obstruction and a person is symptom free of coronary disease.
FIG. 2A to 2C illustrate different views of a diseased artery with atherosclerotic occlusive plaque and a vulnerable plaque. As shown in a longitudinal section of the diseased artery in FIG. 2A, a narrowed arterial lumen 201 is caused by the presence of occlusive atherosclerosis. Atherosclerotic plaque 205 accumulates to impede and reduce blood flow through the arterial lumen and causes symptoms (e.g., angina pectoris). Narrowing of the arterial lumen is also shown in FIG. 2B which is taken at a cross-section AA of the FIG. 2A. The occlusive plaque deposits onto the lining of the artery and reduces the size of the arterial opening, thus limiting the cross-sectional area in which blood can flow through. In cases of typical coronary disease, besides the occlusive plaque that gathers along the lining of the artery, there are other changes that take place in the various layers of the arterial vasculature such as inflammation and increase in macrophages. Physical change in the artery is also observed. An enlargement of the artery, also known as positive remodeling, results from changes in the media and adventitia to enlarge the entire cross-section of the artery to adapt to the narrowing of the lumen by trying to allow the same amount of blood to flow through.
Also in FIG. 2A, downstream of the occlusive plaque 205, relative to the direction of blood flow 209, is a vulnerable plaque of the fibroatheroma type. The vulnerable plaque is represented by a fibrous cap 203 and a lipid core 202. Compared to an occlusive lesion which can easily be detected by an angiogram, the vulnerable plaque is much more difficult to detect. The lipid core 202 develops mostly within the arterial wall with minimal occlusive effects while the fibrous cap 203 surrounds and covers the lipid core 202, separating the lipid content of the core from the blood flow in the arterial lumen. As described above, in the presence of disease, the vessel responds with a “positive remodeling” phenomenon in attempt to maintain constant blood flow. In this case, the fibroatheroma vulnerable plaque has grown into the positively remodeled arterial wall limiting manifestations of vessel occlusion. FIG. 2C shows the vulnerable plaque in the cross-section BB of FIG. 2A. The lipid core 202 has grown into the intimal elastic lamina and merely shielding its thrombogenic contents from the blood stream by the fibrous cap 203.
Autopsy studies and other evidence strongly suggest that the presence of a current acute coronary syndrome (ACS) event and/or existing thrombus at certain plaque sites correlates to predicting a future ACS event in a given patient. The latter indicates the likelihood of a prior thrombotic event (e.g., fibroatheroma rupture) after which the plaque was able to heal itself, or complete occlusion of the vessel was somehow prevented. Autopsy studies also indicate that it is reasonable to expect that at least one vulnerable plaque could exist in each of the majority of catheterization laboratory patients being treated for arterial blockage from visible, occlusive atherosclerosis. Therefore, many of the patients at high risk for future ACS events may already be receiving interventional treatment. With the advancement of new diagnostic techniques, detection of vulnerable plaques is improving. Treating both the occlusive plaques and the vulnerable plaque in one procedure might be beneficial and desirable compared to separate treatments. The key to treat vulnerable plaque is to stabilize the vulnerable plaque and reduce the likelihood of rupture. Conventional stenting has been used to prevent plaque rupture. A more direct means of stabilizing the fibrous cap and thus the vulnerable plaque would provide a more reliable treatment.